Given these results, some patients may receive extended durations of DAPT if they
have a previous history of prior MI, or are post-PCI and have received a DES.
Historically, agents used in the treatment of patients with chronic stable angina
primarily affected either determinants of myocardial oxygen supply, myocardial
oxygen demand, or both. Within this paradigm, β-blockers, CCBs, and chronic nitrate
therapy have demonstrated effectiveness in the prevention of ischemic symptoms. In
January 2006, the US Food and Drug Administration (FDA) granted approval to
ranolazine, representing the first new class of agents to be approved for the treatment
of chronic stable angina in the last 20 years. Unlike traditional anti-anginal
medications, ranolazine does not affect heart rate or BP. The selection of specific
anti-ischemic pharmacotherapy for patients with chronic stable angina should take
into account relevant patient characteristics as well as guideline recommendations.
β-Blockers lower myocardial oxygen demand primarily by lowering heart rate and
myocardial contractility. Neither β-selectivity nor the presence of α-1 blockade
appear to vary efficacy at preventing ischemia and, therefore, the choice of a specific
agent for a given patient will likely depend on cost, number of daily doses, and the
presence of other comorbid conditions. β-Blockers with intrinsic sympathomimetic
activity are not routinely used in patients with stable angina due to reduced efficacy.
The dose of the β-blocker should be titrated to a goal resting heart rate of 55 to 60
beats/minute and therefore will be patient specific.
34 β-Blockers should be avoided
in patients with primary vasospastic angina and may worsen symptoms in patients
with reactive airway disease or PAD. The most common side effects observed with
chronic therapy include bradycardia, hypotension, fatigue, and sexual dysfunction.
Other conditions that may prevent the use of β-blocker therapy include severe
bradycardia or atrioventricular (AV) nodal conduction defects.
Nitrates are available in a number of different formulations and available options are
listed in Table 12-4. Regardless of the formulation, all nitrate options are effective at
preventing or relieving ischemic symptoms if used appropriately, including the use of
a nitrate-free interval. Nitrates can increase myocardial oxygen supply through
vasodilation of the coronary arteries, as well as reduce myocardial oxygen demand
through the reduction of preload. Nitrates produce vasodilation through the
biotransformation and the release of NO.
38 Long-acting nitrates are effective agents
for the prevention of anginal symptoms. Sublingual NTG is a vital agent to treat acute
anginal attacks. Common side effects of nitrate therapy include hypotension,
dizziness, and headache. Headache often will resolve with continued therapy and
may be treated with acetaminophen. Concomitant administration with
phosphodiesterase type 5 inhibitors (within 24 hours for sildenafil and vardenafil, 48
hours for tadalafil) is contraindicated due to the risk of life-threatening
CCBs are highly diverse compounds. They differ markedly in chemical structure as
well as specificity for cardiac and peripheral tissue. Using these characteristics, it is
possible to classify CCBs into several major types (Table 12-5).
Both non-dihydropyridine CCBs (non-DHP CCBs), diltiazem and verapamil, exert
similar effects on myocardial and peripheral tissue. They slow conduction and
prolong the refractory period in the AV node (see Chapter 15, Cardiac Arrhythmias).
Both agents can depress myocardial contractility and are moderate peripheral
vasodilators and potent coronary artery vasodilators.
In contrast to diltiazem or verapamil, the dihydropyridines (DHPs) such as
nifedipine, amlodipine, felodipine, isradipine, and nicardipine do not slow cardiac
conduction. They are more potent peripheral vasodilators and may be associated
with a reflex increase in the heart rate. All DHPs have negative inotropic effects in
vitro, but these effects, clinically, are overshadowed by the reflex sympathetic
activation and decreased afterload. The net effect of these actions results in no or
minimal depression of myocardial function (see Chapter 14, Heart Failure).
Both DHP and non-DHP CCBs produce an increase in myocardial oxygen supply
through vasodilation of the coronary arteries, as well as reduce myocardial oxygen
demand through lowering of intramyocardial wall tension (by lowering systemic BP).
However, non-DHP CCBs would be expected to lower myocardial oxygen demand
to a greater degree because of additional reductions in heart rate and contractility.
Although defined as being within the same pharmacologic class, it is important to
consider DHPs and non-DHPs separately when considering their use in patients with
chronic stable angina. The reductions in heart rate and contractility with non-DHPs
may be beneficial for some patients, although detrimental in others such as patients
with compromised left ventricular (LV) function or bradycardia at baseline.
Conversely, amlodipine and felodipine have been shown to be safe to use in patients
with LV dysfunction and to provide a reasonable option for the prevention of
ischemic symptoms in those patients.
40 CCB should be used cautiously when used in
combination with cyclosporine, carbamazepine, lithium, amiodarone, and digoxin.
Non-DHP CCB should be avoided in most situations due to the duplicate effects on
heart rate and cardiac contractility.
1 Side effects of CCB therapy depend on the
specific agent used. Use of non-DHP CCBs may result in bradycardia, hypotension,
and AV block. Patients receiving DHP CCBs may experience reflex tachycardia,
peripheral edema, headache, and hypotension.
Ranolazine is an anti-ischemic agent that inhibits the late sodium current, thereby
reducing intracellular sodium. During myocardial ischemia, sodium influx is
increased, leading to intracellular calcium overload through the sodium/calcium
exchanger. An excess of intracellular calcium leads to changes that promote and
worsen ischemia, such as increased intramyocardial wall tension and reduced
between ranolazine and traditional antianginal agents is that it has no appreciable
effect on heart rate and BP. The lack of significant hemodynamic effects makes the
drug useful in patients in need of further antianginal therapy but who have low BP or
heart rates preventing titration of conventional antianginal agents.
Commonly Prescribed Organic Nitrates
NTG SL 10–30 minutes 1–3 0.4–0.6 mg
NTG Translingualspray 10–30 minutes 2–4 0.4 mg/metered spray
c 1–2 Initially 5 mcg/minute. Increase every
3–5 minutes until pain is relieved or
NTG SR capsule 4–8 hours 30 6.5–9 mg every 8 hours
e 4–8 hours 30 1–2 inches every 4–6 hours
NTG Transdermal patch 4–>8 hours 30–60 0.1–0.2 mg/h to start; titrate up to 0.8
NTG Transmucosal 3–6 hours 2–5 1–3 mg every 3–5 hours
ISDN SL 2–4 hours 2–5 2.5–10 mg every 2–4 hours
Chewable 2–4 hours 2–5 5–10 mg every 2–4 hours
Oral 2–6 hours 15–40 10–60 mg every 4–6 hours
SR capsule 4–8 hours 15–40 40–80 mg every 6–8 hours
7–8 hours 30–60 10–20 mg BID (morning and midday)
to start; titrate to 20–40 mg BID
8–12 hours 30–60 60 mg every day to start; titrate to
assistance should be summoned.
cDuration after infusion discontinued.
preparations. Also, continued daily use leads to rapid development of tolerance (see note f).
fingers or eyes to prevent headache or hypotension.
Okay to cut Indur in half, do not crush or chew.
BID, 2 times daily; ISDN, isosorbide dinitrate; ISMN, isosorbide monohydrate; IV, intravenous; NTG,
nitroglycerin; SL, sublingual; SR, sustained-release.
Initial clinical trials demonstrated that ranolazine was an effective agent at
reducing anginal episodes when added to existing therapy with CCBs or long-acting
nitrates. Subsequent investigations demonstrated long-term safety and efficacy, and
the agent may be considered at any stage in the treatment of chronic stable angina.
Common adverse effects include headache, constipation, dizziness, and nausea. The
drug is extensively metabolized in the liver through both cytochrome P-450 enzymes
CYP3A4 and CYP2D6; therefore, attention should be paid to potential drug
interactions. CYP3A4 appears to be the major pathway for metabolism and use of
ranolazine is contraindicated in patients with significant hepatic dysfunction and in
those receiving potent inhibitors and inducers of CYP3A4 such as ketoconazole or
rifampin, respectively. Ranolazine is contraindicated in patients receiving many of
the available antiretroviral agents.
Revascularization of the myocardium, with CABG or PCI, is a mainstay in the
treatment of patients with CAD. The goals of revascularization do not differ from the
overall goals in treating patients with chronic stable angina, namely, to relieve
symptoms, improve quality of life, and prevent MI and death. Historically, a great
deal of focus was devoted to comparing CABG, PCI, and medical management and
their relative efficacy in relieving symptoms and improving prognosis. In a broad
population of patients with CAD, revascularization with either CABG or PCI was
found to be superior to medical management therapy alone at relieving symptoms at 1
year, although there was no difference in overall mortality between the treatment
42 However, CABG therapy tended to be superior at providing long-term
relief of symptoms, as well as providing a lower need for repeat revascularization
therapy compared to PCI. When considering subgroups of patients with more severe
disease or who have manifested left ventricular dysfunction, differences in long-term
mortality can be observed among the different treatment strategies. In patients with
double-vessel or triple-vessel disease, significant disease of the left main artery, or
left ventricular dysfunction, CABG therapy has been demonstrated to provide a
reduced 5-year mortality rate compared with PCI or medical therapy alone.
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